PSA Screening revisited
BOSTON, MASSACHUSETTS. Dr. Michael Barry of the Harvard Medical School and the Massachusetts
General Hospital provides an excellent review of the current status of PSA screening for prostate cancer.
Dr. Barry starts out by posing the question "Should a 65-year-old man with no risk factors for prostate
cancer except his age and with a normal digital rectal examination undergo a PSA (prostate-specific-
antigen) test?" Dr. Barry points out that whether or not to have a PSA test is controversial because of the
following:
- No randomized clinical trials have ever demonstrated that early detection and aggressive treatment of
prostate cancer reduce mortality;
- The treatments usually mobilized after a positive PSA test and biopsy (radical prostatectomy,
radiation therapy or castration) are associated with severe side effects including impotence and
incontinence.
He also emphasizes that the PSA test is not that accurate. A recent large-scale trial showed that using a
cut-off point of 4.0 ng/mL would pick up 46 per cent of cancers that would occur within the next ten years
with an accuracy of 91 per cent. The average age of the test group was 63 years. Among older men with
benign prostatic hyperplasia (enlarged prostate) the accuracy may be as low as 54 per cent leading to
many unneeded biopsies and much unwarranted anxiety. It is estimated that 75 per cent of men
undergoing a prostate biopsy because they have PSA levels between 4 and 10 ng/mL do not have
cancer. On the other hand, there is also a 10 per cent chance of harbouring cancer even though the
biopsy shows nothing.
There are currently at least two large-scale trials underway to determine whether PSA screening is
beneficial or harmful overall. However, the results of these trials are not expected until the year 2009. In
the meantime Dr. Barry recommends that men aged 50 to 75 years of age (with no established risk
factors) should be made aware of the availability of the PSA test and its potential harms and benefits so
that they can make an informed choice about having the test. They should receive information on the
following points:
- the likelihood that prostate cancer will be diagnosed;
- the possibilities of false negative and false positive results;
- the anxiety associated with a positive test;
- the uncertainty regarding whether screening reduces the risk of death from prostate cancer.
Several studies have shown that providing this information significantly reduces the proportion of men
who decide to be tested.
Barry, Michael J. Prostate-specific-antigen testing for early diagnosis of prostate cancer. New England
Journal of Medicine, Vol. 344, May 3, 2001, pp. 1373-77
Should men be screened for prostate cancer?
MONTREAL, CANADA. Physicians in North America are becoming increasingly
enthusiastic about screening men for prostate cancer. Prostate cancer is now
the second most common cancer among Canadian men and is second only to lung
cancer in cancer mortality. The two screening tests commonly used are the
digital rectal examination (DRE) and the prostate-specific antigen (PSA)
blood test. Recently some doctors have been warning against the wholesale
use of screening tests. Dr. Kenneth Marshall of the Queen Elizabeth Hospital
in Montreal emphasizes that obtaining the patient's informed consent prior to
testing is essential. This is because the PSA test in particular often gives
a false reading. This can lead to dangerous, invasive biopsies, and
subsequent even more dangerous surgery and radiation treatment. It is
estimated that 30 per cent of men undergoing radical prostate surgery become
impotent, five to six per cent become incontinent and about one per cent die
of the operation. Dr. Marshall concludes there is, as yet, no evidence that
screening for prostate cancer actually saves lives - a view supported by many
European urologists. He also points out that screening and biopsies may
actually do more harm than good in cases where the tumor might have remained
dormant or only grown very slowly.
Marshall, Kenneth G. Screening for prostate cancer. Canadian Family
Physician, Vol. 39, November 1993, pp. 2385-90
Prostate cancer reaching epidemic proportions
LONDON, ENGLAND. More than 100,000 new cases of prostate cancer are now
detected in the U.S.A. and about 33,000 American men die from this disease
each year. In the U.K. prostate cancer claimed 9,400 lives in 1992. The
cause of the rise in cases is unknown. Alcohol and smoking are not
implicated, but diet may well be. Thus the incidence amongst men eating a
typical western diet is about 100 per 100,000 as compared to 6 per 100,000 in
the Far East. Many men are unaware that they have a prostate tumour. As a
matter of fact, latent prostate cancers are found in more than 70% of men
over the age of 80, but are not the cause of their death. Recent publicity
in the U.S.A., fuelled by the treatment of Senator Robert Dole for prostate
cancer, has heightened the awareness of the disease. The total research
budget for prostate cancer in the U.S.A. has been increased from $10 million
to $24 million annually and all men are now advised to have a rectal
examination and a PSA (prostate specific antigen) test every year. While
this is expected to detect about 30 to 40% more cancers some medical doctors
are sounding a warning: many men have no complications from their prostate
tumour and go on to die of unrelated causes - is it right to affect the
quality of their lives by telling them that they have prostate cancer?
Siddall, Rhonda. Time to screen for prostate cancer? New Scientist,
February 6, 1993, pp. 27-30
Is screening for prostate cancer worthwhile ?
TORONTO, CANADA. The controversy over the benefits of screening for prostate
cancer rages on. Now researchers at the University of Toronto have concluded
that testing men with no overt symptoms of prostate cancer is inadvisable.
They found that screening often precipitates invasive procedures and that the
overall effect on quality of life is negative. Specifically, they found that
a one-time screening with prostate-specific antigen (PSA) or transrectal
ultrasound (TRUS) resulted in only a very small increase in life expectancy
in randomly selected men between 50 and 70 years of age. The increase in
life expectancy was far outweighed by a net loss in the quality of life due
to complications (impotence, incontinence, rectal injuries) occurring during
invasive testing procedures and surgery. Screening with a digital rectal
examination (DRE) produced no reduction at all in mortality from prostate
cancer.
Krahn, Murray D., et al. Screening for prostate cancer: a decision analytic
view. Journal of the American Medical Association, Vol. 272, No. 10,
September 14, 1994, pp. 773-80
Are prostate cancer rates really growing?
DETROIT, MICHIGAN. The incidence of prostate cancer has seemingly grown
rapidly in recent years. In the Detroit area an increase in invasive
prostate cancer of 72 per cent has been observed between 1988 and 1991.
Researchers at the Michigan Cancer Foundation now believe that the observed
increase is due not to the fact that more men get prostate cancer, but rather
to a much more widespread use of the prostate-specific antigen (PSA) test.
They point out that the use of the PSA test almost quadrupled in the period
1990 to 1992. This rise in test volume is paralleled by a dramatic increase
in the rate of radical prostate surgery (prostatectomy) which also quadrupled
in the Detroit area between 1987 and 1991. The researchers believe that the
"rise" in prostate cancer with the advent of the PSA test is analogous to the
"rise" in breast cancer coinciding with the widespread use of mammography.
They also point out that the benefit of aggressive local therapy such as
prostatectomy as a cure for prostate cancer remains uncertain.
Demers, Raymond Y., et al. Increasing incidence of cancer of the prostate.
Archives of Internal Medicine, Vol. 154, June 13, 1994, pp. 1211-16
Screening for prostate cancer not recommended
HOUSTON, TEXAS. Over 165,000 new cases of prostate cancer were diagnosed
among men in the United States in 1993 and 35,000 died from the disease. The
increased use of screening tests has long been advocated by the medical
community as a means of lowering the death toll. Now researchers at the
University of Texas have reached the clear conclusion that periodic screening
of men with no other symptoms of prostate cancer is not recommended. They
base their conclusion on the fact that there have never been any medical
trials which showed that early diagnosis increases length of survival or
quality of life. Early detection of microscopic cancers may lead to invasive
biopsies and treatments which in turn can result in impotence, incontinence
and even death. A recent study found that even with the "best possible"
treatment (radical prostatectomy and radiation) a patient with a nodule
identified by DRE (digital rectal examination) would have been better off if
the nodule had been left alone. Other studies have shown that watchful
waiting is a reasonable clinical management strategy if a prostate nodule is
found. The researchers conclude that when quality-of-life factors are
considered, screening men for prostate cancer is not indicated.
Cantor, Scott, B., et al. Prostate cancer screening: a decision analysis.
The Journal of Family Practice, Vol. 41, No. 1, July 1995, pp. 33-41
Cancer screening comes under increasing scrutiny
BOSTON, MASSACHUSETTS. Many cancer researchers are becoming concerned about
the development of more and more sophisticated screening tests. Professor
Suzanne Fletcher, MD of the Harvard Medical School says "Our tests and
technology may have outstripped our ability to distinguish lesions that look
like cancer under the microscope but don't act like it." Other researchers
point out that 50 per cent of men have signs of prostate cancer, but
nevertheless die from other causes. Similarly, 20 to 30 per cent of women
have signs of breast cancer when autopsied but only 3 to 4 per cent of all
women actually die of breast cancer. The criticism is particularly heavy
when it comes to the prostate-specific antigen (PSA) test. Dr. Barnett
Kramer, MD of the National Cancer Institute points out that the rate of
prostate cancer diagnosis is going up faster than any other cancer on record
and the rate of prostate surgery (prostatectomy) is following right along.
Complications of impotence, incontinence, and bowel dysfunction after surgery
"are on the order of tens of percents" says Dr. Robert Nease of the
Washington University Medical School in St. Louis. Dr. Nease concludes
"That's a pretty steep price to pay for unproven benefits."
Holzman, David. Screening tests pick up too many indolent cancers. Journal
of the National Cancer Institute, Vol. 87, No. 20, October 18, 1995, pp.
1506-07
Accuracy of PSA test questioned
DALLAS, TEXAS. The PSA (prostate-specific antigen) test is commonly used to
screen men for prostate cancer. A PSA level of greater than 4.0 ng/mL is
generally considered indicative of possible prostate cancer and often
triggers an invasive and potentially dangerous biopsy (transrectal
ultrasound-guided prostate biopsy). Now researchers at the Dallas Veterans
Affairs Medical Center report that a single PSA test may not be reliable
enough to serve as a basis for the biopsy decision. Their study involved 295
men who had had a PSA test twice within a period of 90 days. The researchers
found that 30 per cent of the patients tested had a PSA difference of more
than 1 ng/mL between the two measurements. They conclude that 10 per cent of
all patients having a single PSA test would be told either that everything
was OK when in fact they might have cancer or be subjected to an unnecessary
biopsy. The researchers recommend that physicians make up their own mind as
to the level of error they are comfortable with and then repeat the test
accordingly. For instance, if a doctor is only willing to accept a 20 per
cent or lower probability of being wrong he would repeat the test if the
first PSA test gave a value between 2.3 and 8.6 ng/mL. If however, he was
willing to accept a 50 per cent risk of being wrong he would only need to
repeat tests with values between 3.5 and 4.9 ng/mL. Further statistical
evaluation of the data collected by the researchers confirmed that PSA values
tend to increase with age from a mean of 1.4 ng/mL between 40 and 50 years of
age to a mean of 3.6 ng/mL for men aged 70 to 80 years. The researchers also
found that a standard digital rectal examination (DRE) correlates quite well
with the PSA test. Men with a normal prostate according to the DRE test had
a mean PSA level of 2.44 ng/mL while men with a suspected cancerous tumor on
the prostate (according to the DRE test) had a mean PSA level of 3.73 ng/mL.
The researchers question the validity of using one standard value (4.0 ng/mL)
as a cutoff point to determine if a biopsy is needed. They suggest that the
cutoff point should depend on the patient's age with 2.5 ng/mL being the
cutoff point for men 40 to 50 years old rising to 6.5 ng/mL for men 70 to 80
years old.
Roehrborn, Claus G., et al. Variability of repeated serum prostate-specific
antigen (PSA) measurements within less than 90 days in a well-defined patient
population. Urology, Vol. 47, No. 1, January 1996, pp. 59-66
More tests lead to more surgery
PORTLAND, MAINE. Physicians have long been puzzled why some areas of the New
England states have very high rates of heart surgery while others have
relatively low rates. Now researchers at the Maine Medical Center report
that the amount of heart surgery (bypass surgery and angioplasty) done in an
area is almost entirely dependent upon how much diagnostic testing is done in
that area. In other words, it bears little or no relation to the actual
prevalence of heart disease. The researchers found a strong linear
relationship between the number of stress tests done in a certain
geographical area and the number of subsequent angiography examinations and
surgical interventions. This relationship could only be explained by
concluding that more testing leads to more surgery. Other New England
researchers have arrived at a similar conclusion and have also discovered
that more mammography leads to more biopsies and more breast surgery, that
more spine x-rays lead to more back surgery, and that more prostate biopsies
and most likely more PSA tests lead to more radical prostatectomies. The
researchers conclude that "how much disease is diagnosed depends on how hard
one looks." They also suggest that physicians should recognize that just as
more therapy may be harmful so may more diagnostic tests. The total Medicare
billings by American physicians in 1993 for diagnosis and treatment of
coronary heart disease exceeded one billion dollars. Medical researchers
estimate that 80 per cent of all angiographic procedures are inappropriate
and that half of all bypass operations performed in the United States are
unneccessary or of no benefit.
Wennberg, David E., et al. The association between local diagnostic testing
intensity and invasive cardiac procedures. Journal of the American Medical
Association, Vol. 275, No. 15, April 17, 1996, pp. 1161-64
Verrilli, Diana and Welch, H. Gilbert. The impact of diagnostic testing on
therapeutic interventions. Journal of the American Medical Association, Vol.
275, No. 15, April 17, 1996, pp. 1189-91
Screening for prostate cancer comes under fire - again!
BRISBANE, AUSTRALIA. The controversy over the routine screening of healthy
men for prostate cancer using the PSA (prostate specific antigen) test
continues. Now Australian medical doctors and researchers have come out
strongly against the practice. The Australian team estimates that if 100,000
men over 50 years of age are screened with the PSA test, about 15,000 will
show a positive result, i.e. possible cancer. These 15,000 men will likely
have a biopsy which, in itself, is by no means without danger. Of the 15,000
about 4,500 will have a positive biopsy result and will presumably be exposed
to further treatment in order to "cure" the cancer. The remaining 10,500
will suffer considerable anxiety while waiting for their biopsy results. The
researchers point out that there has been no scientifically valid studies
which prove that treatment is more beneficial than no treatment or that
screening can extend or improve quality of life. The preferred treatments,
however, have very serious side effects. It is estimated that 60 to 90 per
cent of men undergoing radical prostatectomy become impotent while 30 to 40
per cent develop some degree of incontinence. Between 40 and 70 per cent of
men exposed to radiotherapy also develop impotence. The researchers suggest
that routine screening for prostate cancer is comparable to screening for
lung cancer. Even though lung cancer kills five times more men than does
prostate cancer nobody advocates a routine screening program for lung cancer
- for the simple reason that no effective treatment is available for this
disease. The researchers conclude that screening men with no other symptoms
of prostate cancer is inadvisable.
In a separate research paper Dr. Brian Cox of the Otago Medical School in New
Zealand echoes the Australians' recommendation and points out that no proper
trials have ever shown that screening has an effect on prostate cancer
mortality. He concludes that recommending asymptomatic patients have a PSA
test is unethical.
Hirst, Geoffrey H.L., et al. Screening for prostate cancer: the case
against. Medical Journal of Australia, Vol. 164, March 4, 1996, pp. 285-
88
Cox, Brian. Prostate cancer screening is experimental. New Zealand Medical
Journal, Vol. 109, March 8, 1996, pp. 63-4
New early warning signal for prostate cancer
BOSTON, MASSACHUSETTS. Researchers at the Harvard Medical School report that
they have discovered a new diagnostic test which will predict men's risk of
prostate cancer years before the cancer actually develops. Their discovery
is part of the ongoing Physicians' Health Study which was started in 1982 and
involves almost 15,000 physicians. By March 1992 520 cases of prostate
cancer had occurred among the physicians. In 152 of these cases enough blood
plasma had been collected in 1982 to perform analyses for the content of IGF-
I (insulin-like growth factor-I). These analyses were done in 1997 and the
results compared to analyses done on 152 plasma samples from 1982 obtained
from physicians without prostate cancer. The researchers found that survey
participants who later developed prostate cancer tended to have higher levels
of IGF-I in their blood than did the controls. Men with IGF-I levels in the
upper quartile (25 per cent) were found to have a 4.3 times greater risk of
developing prostate cancer than did men with levels in the lower quartile of
results. On average, there was a seven-year lag between the appearance of a
high IGF-I level in the blood samples and the actual diagnosis of prostate
cancer. The importance of high IGF-I levels was found to be particularly
significant for men over 60 years of age. In this age group men with IGF-I
levels in the highest quartile were almost eight times more likely to later
develop prostate cancer than were men with levels in the lowest quartile. It
is interesting to note that many of the men with elevated IGF-I levels who
later developed prostate cancer had normal PSA levels (less than or equal to
4 ng/ml) when the blood samples were collected. The researchers conclude
that IGF-I levels may serve as an early warning signal for prostate cancer in
much the same way as high cholesterol levels serve as an early warning for
atherosclerosis and heart disease. They also raise concern that
administration of growth hormone and specifically IGF-I to delay the effects
of aging in older men may increase the risk of prostate cancer. Other
researchers (data still unpublished) have found an equally strong link
between IGF-I levels and the risk of breast cancer and are currently
investigating an association with colon cancer.
Chan, June M., et al. Plasma insulin-like growth factor-I and prostate
cancer risk: a prospective study. Science, Vol. 279, January 23, 1998, pp.
563-66
Barinaga, Marcia. Study suggests new way to gauge prostate cancer risk.
Science, Vol. 279, January 23, 1998, p. 475